Monoclonal antibodies (mAbs) play significant roles in the chemotherapeutic treatment of cancer. In an effort to extend their therapeutic potential, we have developed novel technologies surrounding antibody-drug conjugates (ADCs). The goal of this work is to utilize mAbs for the specific delivery of highly cytotoxic drugs to cancer cells, while sparing normal tissues from chemotherapeutic damage. The key parameters in developing an active and well tolerated ADC are the selectivity profiles of the mAb, the potency and stability of the cytotoxic payload, the conditional stability of the linker used to attach the drug to the mAb, and the technology used to control the site and stoichiometry of drug attachment. This presentation will overview how all of these issues were taken into account, leading to the development of ADCETRIS (SGN-35, brentuximab vedotin), a potent ADC that is now clinically approved for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma.

Development of a potent antibody drug conjugate for the clinical treatment of CD-30 positive malignancies

243rd National Meeting (2012)

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